Objective: The study’s aim was to gain insights into factors influencing sustainable return to work following total knee arthroplasty (TKA). Design: A descriptive multiple-case design was used. A case was defined as a worker’s following TKA work disability situation. Settings: The cases came from public hospitals in urban and semi-urban areas in Quebec (Canada) and involved mostly non-work-related TKAs. Subjects: Workers had to be between 6 and 12 months post-TKA, have physical/manual jobs and currently employed. Their rehabilitation professionals and workplace representatives (employer and/or union) were also recruited, based on the work disability paradigm. Main measures: Semi-structured interviews, questionnaires on pain, physical work demands (workers only), and observation of the work activities of those workers back at work were used. Cases were compared and categorized for worker-perceived levels of difficulty in returning to or staying at work: little or no difficulty ( n = 8); some difficulty ( n = 5); not back at work due to excessive difficulty with their knee ( n = 4). Results: A total of 17 cases were constituted. In only one case, the worker benefitted from an interdisciplinary work rehabilitation approach. Results highlight the interplay among these factors: (1) the workers’ perceptions of their residual symptoms and ability to manage them, (2) the interaction between work adjustments and tools offered by the employers and the workers’ own strategies, and (3) perceptions of the workers’ physical capacities. Conclusion: Workers’ who face high levels of work demands/difficulties and who have limited access to work adjustments and tools should be referred for work rehabilitation.